e76 Abstracts

counts within the environment. The Trigger Line, set at 2standard deviations above the mean, would traditionallyindicate the level at which investigation into infectioncontrol for MRSA or Clostridium difficile was warranted.However, the same principles of control may be used tohelp ensure that appropriate measures are being main-tained to provide a safe environment for patients at riskof invasive fungal infection. This has now become a contin-uous process with results from routine monthly air samplingbeing incorporated into the SPC charts.

Conclusions

Statistical process control charts are a useful addition toenvironmental control measures to provide optimal airquality within clinical areas housing immunocompromisedpatients at risk of invasive fungal infection.

VORICONAZOLE TREATMENT OF CRYPTOCOCCALMENINGITISCATEGORY: SCIENTIFIC FREE PAPER

Adam Jeans, Andrew Ustianowski, Javier Vilar,Ed WilkinsMonsall Unit, Department of Infectious Diseases & TropicalMedicine, North Manchester General Hospital, Manchester,United Kingdom

Introduction

Amphotericin B, given in conjunction with flucytosine, isestablished as first line therapy for the induction phase ofcryptococcal meningitis treatment. IDSA guidelines recom-mend this is followed by a consolidation phase of treatmentwith 8 weeks of fluconazole 400mg daily before commenc-ing maintenance therapy with fluconazole 200mg. Althoughno agreed breakpoints exist for in-vitro susceptibility test-ing of Cryptococcus species, using CLSI methodology a fluco-nazole MIC of � 16mg/ml has been associated with a worseclinical outcome in some studies. Itraconazole is an alterna-tive to fluconazole but penetrates poorly into CSF and is as-sociated with a higher risk of relapse when used asmaintenance therapy. Voriconazole is structurally relatedto fluconazole and can achieve therapeutic levels of drugwithin the CSF with standard dosing. Despite its availabilityas an oral formulation, experience with voriconazole in thetreatment of cryptococcal meningitis has been limited. Wereport three cases in which voriconazole was used as con-solidation or maintenance therapy in the setting of an ele-vated fluconazole MIC.

Scientific findings

Three cases of cryptococcal meningitis had been treated inour unit using voriconazole by July 2010. Two cases wereHIV positive, with CD4 counts at presentation of 21 and 3

cells/mm3. The first had a previous history of cryptococco-sis and took fluconazole maintenance therapy. The thirdcase was HIV negative but received immunosuppressivetreatment for rheumatoid arthritis. All cases had Crypto-coccus neoformans isolated from CSF. MICs for fluconazolewere 32, 8 and 16mg/ml, with voriconazole MICs of 0.5,0.25 and 0.5mg/ml respectively. Each patient received atleast two weeks of ambisome and flucytosine before chang-ing treatment to oral voriconazole.

Discussion

Voriconazole was well tolerated in all three cases. Both HIVpatients required changes to their antiretroviral regimebecause of the interaction with protease inhibitors, and allcases had therapeutic drug monitoring performed to titratetheir voriconazole dose. The first case was complicated bychronic microsporidial diarrhoea and their cryptococcaldisease relapsed in association with sub-therapeutic vor-iconazole levels after 8 months of treatment. The repeatisolate showed similar susceptibility results and the patientresponded to retreatment. The other two cases receivedvoriconazole during the consolidation phase and showed nosigns of relapse at 5 months following their diagnosis.

Conclusions

Voriconazole can be effective as consolidation and main-tenance therapy for the treatment of cryptococcal menin-gitis in the setting of an elevated fluconazole MIC.

Therapeutic drug monitoring is essential when voricona-zole is co-administered with other therapies and thepotential for drug-drug interaction is present.

USE OF STEROIDS IN THE MANAGEMENT OF LIVERABSCESSES IN CHRONIC GRANULOMATOUSDISEASECATEGORY: CLINICAL LESSON

Lukman Hakeem, David WilksReigonal Infectious Diseases Unit, Edinburgh, UnitedKingdom

Introduction

Chronic Granulomatous Disease (CGD) is a rare geneticallyheterogeneous primary immunodeficiency affecting intra-cellular killing by phagocytes, leading to recurrent andpersistent bacterial and fungal infections with formation ofgranulomata. A range of defects in the NADPH oxidativeenzyme complex have been identified.

Here we describe a young man with CGD presenting withstaphylococcal liver abscesses unresponsive to appropriateantibiotic therapy, where steroids were used resulting ina favourable outcome. Systemic steroids may thereforehave an important role in the management of patients withCGD with infective complications.

Abstracts e77

Scientific findings

A 28-year old with CGD and a history of recurrent infectionswas admitted with fever and raised inflammatory markers.He had been relatively free of infections for 10-years priorto admission and was on co-trimoxazole prophylaxis.

An MRI-scan confirmed multiple liver abscesses. Staphy-lococcus aureus was isolated from abscess fluid. He wascommenced on antibiotics, itraconazole and interferon-gamma, and was assessed for liver transplantation whenhis condition failed to improve. Addition of prednisoloneto treatment resulted in a steady recovery with a fall in in-flammatory markers, and radiographic resolution of ab-scesses over a period of 12-months. He is currentlyasymptomatic.

Discussion

Patients with CGD are at risk of recurrent bacterial andfungal infections, predominantly pneumonia. Liver ab-scesses occur in approximately 25% of cases, mostly dueto staphylococci. Aggressive surgical management wasdifficult in this case due to the size, site and multiplicityof lesions although recommended.

Corticosteroids are used for obstructive complications ofCGD and their use in refractory infections has beenreported in case studies. In our case antibiotic therapycombined with interferon gamma did not lead to resolutionof the abscesses, but addition of steroids resulted inresolution of fever, significant improvement in inflamma-tory markers and radiological appearance.

Conclusions

Corticosteroids are potent anti-inflammatory agents thatinhibit granuloma formation. Anecdotal reports of benefitin CGD associated liver abscesses have been published. Thiscase supports the belief that steroids should be added toantibiotic therapy, particularly in cases where surgery iscontraindicated.

OPTIMISING STRATEGIES FOR MALARIAELIMINATION: PRIMAQUINE, MASS DRUGADMINISTRATION AND ARTEMISININRESISTANCECATEGORY: SCIENTIFIC FREE PAPER

Richard Maude 1,2, Duong Socheat 3, Chea Nguon 3,Shunmay Yeung 4, Lisa White 1

1Mahidol-Oxford Tropical Medicine Research Unit, Facultyof Tropical Medicine, Mahidol University, Bangkok,Thailand2Centre for Tropical Medicine, Nuffield Department ofClinical Medicine, CCVTM, University of Oxford, ChurchillHospital, Oxford, United Kingdom3Cambodia National Malaria Centre, Phnom Penh,Cambodia4 London School of Hygiene and Tropical Medicine, London,United Kingdom

Introduction

A recent field study in Cambodia demonstrated dramaticreductions in malaria parasite prevalence following theintroduction of new antimalarial drugs. This study em-ployed multiple combined strategies and it was not clearwhich of these were the main contributors to the re-ductions. A mathematical model was developed and vali-dated against this field data. This model was used toanalyse the results of the trial in detail.

Scientific findings

Themodelling demonstrated that themaincontributor to theinitial reduction of malaria prevalence in this study was theuse of mass drug administration (MDA) with artemisinincombination therapy (ACT). The subsequent continued de-cline in parasite prevalence and elimination in some of thevillageswas found tobedue to introducing high coverageACTfor treatment. Primaquine, in the form ofMDAwith repeateddoses or adjunctive treatment with a single dose, signifi-cantly further reduced prevalence. The model was used todesign optimal elimination strategies and explore key policyimplications in the context of artemisinin resistance.

Discussion

Main policy implications:

� Switching treatment of clinical cases to high cov-erage and compliance with ACT produces long-term reduction in prevalence whereas MDA alonedoes not

� Primaquine enhances the effect of ACT andreduces the spread of artemisinin resistance

� Sustained efforts are crucial for successfulelimination

� Parasite prevalence is a better surveillance mea-sure for elimination programmes than numbersof symptomatic cases

Conclusions

Mathematicalmodellingwhen validated by good quality fielddata can combine information from diverse sources and beused as a tool for enhanced analysis to provide new insightsinto the results of clinical studies, tomake predictions and toassist with planning future studies. This study has providedpredictions and a number of novel insights which will be ofdirect practical benefit to assist planning of future malariaelimination strategies, particularly in the context of thenewly emerging artemisinin resistance.

AN AUDIT OF THE MANAGEMENT OFSTAPHYLOCOCCUS AUREUS BLOODSTREAMINFECTIONS OVER TWO YEARS IN A DISTRICT